CD40-L Blockade for Prevention of Acute Graft-Versus-Host Disease
1 other identifier
interventional
45
1 country
3
Brief Summary
The purpose of this study is to examine the safety and efficacy of the addition of BMS-986004 to standard of care Sirolimus (SIR)-based immune suppression.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Feb 2019
Longer than P75 for phase_1
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 20, 2018
CompletedFirst Posted
Study publicly available on registry
July 30, 2018
CompletedStudy Start
First participant enrolled
February 15, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 25, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
July 25, 2023
CompletedApril 2, 2026
March 1, 2026
4.4 years
July 20, 2018
March 31, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Incidence of Grade II-IV Acute Graft-versus Host Disease
Cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) by day 100 after hematopoietic cell transplantation (HCT). Acute GVHD severity will be determined by standard Consensus Criteria, and the cumulative incidence of grade II-IV acute GVHD will be reported through day 100 post-HCT, with relapse and death as competing risk events.
1 year post HCT
Secondary Outcomes (4)
Chronic Graft-versus Host Disease Through 1 Year Post HCT
1 year post HCT
Malignancy Relapse Post-HCT
1 year post HCT
Non-relapse Mortality
1 year post HCT
Overall Survival (OS)
1 year post HCT
Other Outcomes (2)
Glucocorticoid Exposure
1 year post HCT
Neutrophil and Platelet Engraftment
1 year post HCT
Study Arms (1)
Combination Therapy
EXPERIMENTALBMS-986004: From day 13, intravenously (IV) every 2 week through day 100 post HCT. Tacrolimus: From day -3 as standard of care. Sirolimus: From day -1 as standard of care.
Interventions
BMS-986004 will be administered in ascending dose cohorts in the phase I component of the trial. Based on prior PK and PD data, dose levels of 225 mg, 675 mg, and 1500 mg (3 total phase I dose levels) will be examined. BMS-986004 will be given intravenously (IV) every 2 weeks, starting from day -3 (i.e., three days prior to HCT) onward through a total of 100 days post-HCT. The maximum tolerated dose (MTD) identified in the phase I component of the trial will be carried forward as the recommended dose level in the phase 1 expansion cohort.
Sirolimus and tacrolimus (standard of care pharmacologic immune suppression) will be given according to institutional standards. Sirolimus (SIR) will be given as a loading dose on day -1 orally, then daily as maintenance therapy with target levels of 10-14ng/mL early post-HCT, then tapered to 5-14ng/mL range. Program standards will be used for SIR and TAC level monitoring frequency and dose adjustments, including careful attention to drug-interactions.
Sirolimus and tacrolimus (standard of care pharmacologic immune suppression) will be given according to institutional standards. In brief, tacrolimus (TAC) will be started on day -3 IV, and transitioned to oral TAC when oral medications are tolerated; target level is 3-7ng/mL. Program standards will be used for SIR and TAC level monitoring frequency and dose adjustments, including careful attention to drug-interactions.
Eligibility Criteria
You may qualify if:
- Hematologic malignancy or blood disorder requiring allogeneic HCT
- Adequate vital organ function as defined per protocol
- Karnofsky Performance Status Score (KPS) ≥ 80%
- Participants must have an available 8/8 HLA-A, -B, -C, and -DRB1 matched-related or unrelated donor
You may not qualify if:
- Active infection not controlled with appropriate antimicrobial therapy
- HIV, hepatitis B or C infection or known history of HIV, hepatitis B or C(all patients will be tested for HIV, hepatitis B and C as part of standard pre-transplant testing, and will be excluded from this trial if positive)
- Anti-thymocyte globulin, or cyclophosphamide administered within 14 days before or planned to receive with HCT conditioning or as part of GVHD prophylaxis in the 14 days after HCT
- Known allergic reactions to components of the study drug
- Concurrent treatment with another investigational drug
- History of thromboembolism, transient ischemic attack, stroke, myocardial infarction within 3 months preceding the transplant, or uncontrolled congestive heart failure or cardiac arrhythmias.
- Post-transplant maintenance therapies such as FLT3 inhibitor, tyrosine kinase inhibitor, JAK inhibitors etc. are not allowed if plan is to initiate such therapies \<90 days post-transplant. Patient will be eligible if plan to initiate maintenance therapy is after day 90 post-transplant.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (3)
City of Hope Cancer Center
Duarte, California, 91010, United States
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Farhad Khimani, M.D.
H. Lee Moffitt Cancer Center and Research Institute
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 20, 2018
First Posted
July 30, 2018
Study Start
February 15, 2019
Primary Completion
July 25, 2023
Study Completion
July 25, 2023
Last Updated
April 2, 2026
Record last verified: 2026-03